The focus of our research project is the study of sensory and signal transduction in the bacterium Myxococcus xanthus as cells form multicellular aggregates and undergo fruiting body development. Directed cell movements in response to self-generated signals are important for the proper- development of all multicellular organisms, including higher eukaryoyes which must transduce signals to coordinate growth and differentiation during embryogenesis. 1. Analysis of components of the "frizzy" signal transduction pathway - We plan to study FrzCD, FrzE, and FrzS. FrzCD, a methylated chemotaxis protein (MCP) receptor, differs from most MCPs in that it is soluble during vegetative growth but associates with the cell membrane in a dynamic manner during early development. We plan to study its structure and unique pattern of localization. We will also study FrzE, a CheA-CheY fusion protein, and search for interacting proteins. FrzS, a protein needed for S-motility, will also be characterized. 2. Characterization of the roles of newly identified Che homologues in M. xanthus - W e have recently discovered two new chemotaxis operons in M. xanthus that encode many Che homologues. We plan to analyze the roles that these new signal transduction pathways play in the complex coordination of multicellular interactions required for development. 3. Search for self-generated signaling molecules required for developmental aggregation The frgA and abcA genes, both of which confer the Frz phenotype when mutated, are most likely involved in the synthesis or transport of self generated chemotaxis signals since the defect in the mutants can be complemented extracellularly. We propose to use this complementation assay to search for and purify the putative signal substances.